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Evidence indicates that noradrenaline elicits anti-inflammatory actions in the central nervous system (CNS), and plays a neuroprotective role where inflammatory events contribute to pathology. Here we examined the ability of pharmacological enhancement of central noradrenergic tone to impact upon activation of the IL-1 system in rat brain. Treatment with the noradrenaline reuptake inhibitor reboxetine combined with the α₂-adrenoceptor antagonist idazoxan induced expression of IL-1β as well as its negative regulators, IL-1 receptor antagonist (IL-1ra) and IL-1 type II receptor (IL-1RII) in rat cortex. The ability of reboxetine/idazoxan treatment to activate the IL-1 system was mediated by β-adrenoceptors, as the aforementioned effects were blocked by the β-adrenoceptor antagonist propranolol. Moreover, administration of the brain penetrant β₂-adrenoceptor agonist clenbuterol induced expression of IL-1β, IL-1ra …